International audit of simulation use in pre-registration medical radiation science training.

INTRODUCTION: Simulation-based education (SBE) can replicate the challenging aspects of real-world clinical environments, while providing a safe and less intimidating setting. Literature supports its use within medical radiation science (MRS) training for safe practice of psychomotor skills, development of problem solving, team working, interpersonal and decision-making skills and embedding awareness of patient safety. This project aimed to quantify usage of SBE resources and activities internationally and to evaluate how this changed during COVID-19 restrictions. METHODS: An anonymous online survey tool gathered data relating to programme demographics, simulation resources, simulation activities and future plans. A link to the survey was distributed to programme leads via social media, professional bodies and national networks. RESULTS: A total of 72 responses were received from a range of countries and representing a range of programme structures. Most respondents reported up to 100 h of SBE per student per year with low fidelity resources and image viewing software featuring most prominently. There was low reported engagement of service users within simulation activities. Respondents also indicated that COVID-19 had been a trigger for rapid uptake of simulation resources. CONCLUSION: SBE forms an important aspect of MRS training internationally with low-fidelity resources being widely deployed. Where available, high fidelity virtual reality and specialised profession-specific resources were used heavily. There was a low level of reported engagement with service users or expert patients in simulation activities. Future research will identify whether the rapid uptake of SBE during COVID-19 continues and clarify the role of service users in SBE provision. IMPLICATIONS FOR PRACTICE: Increased collaboration between MRS education providers may help to improve parity of SBE provision and identify additional opportunities to engage service users within SBE.

Bridging disciplines to advance elasmobranch conservation: applications of physiological ecology.

A strength of physiological ecology is its incorporation of aspects of both species' ecology and physiology; this holistic approach is needed to address current and future anthropogenic stressors affecting elasmobranch fishes that range from overexploitation to the effects of climate change. For example, physiology is one of several key determinants of an organism's ecological niche (along with evolutionary constraints and ecological interactions). The fundamental role of physiology in niche determination led to the development of the field of physiological ecology. This approach considers physiological mechanisms in the context of the environment to understand mechanistic variations that beget ecological trends. Physiological ecology, as an integrative discipline, has recently experienced a resurgence with respect to conservation applications, largely in conjunction with technological advances that extended physiological work from the lab into the natural world. This is of critical importance for species such as elasmobranchs (sharks, skates and rays), which are an especially understudied and threatened group of vertebrates. In 2017, at the American Elasmobranch Society meeting in Austin, Texas, the symposium entitled `Applications of Physiological Ecology in Elasmobranch Research' provided a platform for researchers to showcase work in which ecological questions were examined through a physiological lens. Here, we highlight the research presented at this symposium, which emphasized the strength of linking physiological tools with ecological questions. We also demonstrate the applicability of using physiological ecology research as a method to approach conservation issues, and advocate for a more available framework whereby results are more easily accessible for their implementation into management practices.

Genetic analysis of ventricular arrhythmia in young German Shepherd Dogs.

BACKGROUND: Ventricular arrhythmias (VA) and sudden death are inherited in German Shepherd Dogs (GSDs). OBJECTIVES: To estimate the genetic parameters (heritabilities and correlations) of 3 traits of VA (single premature ventricular complexes (PVCs), 2 consecutive PVCs (couplets), and 3 or more consecutive PVCs-ventricular tachycardia [VT]). ANIMALS: Three hundred and ninety-eight GSDs. METHODS: Prospective, observational, case control study. Dogs were phenotyped by 24-hour ambulatory ECG from 6 to 45 weeks of age. Edited ECG records included the number of incidents of (1) single PVCs, (2) couplets, and (3) VT. RESULTS: A data set of 1,239 Holter records from 398 GSDs was used to estimate genetic variables. Phenotypic correlations for affectedness (binarily coded 0/1) of the 3 traits ranged from 0.55 to 0.74, whereas correlations for severity (continuous values of 24-hour VA counts) ranged from 0.26 to 0.39. Estimates of genetic correlation among the severity traits were 0.06 to 0.27. Estimated heritabilities were 0.54, 0.54, and 0.46 for affectedness and 0.33, 0.69, and 0.69 for severity of PVCs, couplets, and VT, respectively. Month and year of birth and age at ECG recording had significant effects on all 3 traits. Season of ECG recording had a significant effect on the number of single PVCs, but not couplets or incidents of VT. Age of onset differed, with single PVCs appearing an average of 4 days earlier than couplets and VT. CONCLUSION: These results imply a strong genetic component for this disease but suggest that differences in the 3 traits should be taken into consideration in studies to identify the underlying genes.

A review of the anatomy of the upper airway in early infancy and its possible relevance to SIDS.

BACKGROUND: Since the danger of prone sleeping in the first 6 months of life has been publicised, there has been a dramatic and consistent reduction in the incidence of sudden infant death syndrome (SIDS). However, unexpected infant deaths and apparent life-threatening events (ALTEs) continue to occur that are clearly not associated with known epidemiological risk factors. AIMS: To review the unique features of the anatomy and function of the upper airway of the young infant which contribute to increased vulnerability to hypoxia in this age group. We discuss the clinical identification of those infants at risk of obstruction or restriction of the upper airway and the management of the 'at risk' infant. CONCLUSIONS: In the era after the "back to sleep" campaigns, it is likely that an increasing proportion of cases of ALTEs and SIDS will be related to obstruction or limitation of upper airway size leading to sleep hypoxia/asphyxia. This type of problem may be anticipated by evaluation and investigation of infants with signs or a clinical history consistent with possible upper respiratory tract compromise, including micrognathia.

Multifactorial genetics of exencephaly in SELH/Bc mice.

BACKGROUND: The SELH/Bc mouse strain has 10-30% exencephaly and is an animal model for human neural tube closure defects. This study examined the number of causative genes, their dominance relationships, and linkage map positions. METHODS: The SELH/Bc strain (S) was crossed to the normal LM/Bc strain (L) and frequencies of exencephaly were observed in the F(1), BC(1), and F(2) generations. 102 F(2) males were individually testcrossed by SELH/Bc. The extremes, the 10 highest and 10 zero exencephaly-producing F(2) sires, were typed for 109 SSLP marker loci in a genome screen. Next, the resultant five provisional chromosomal regions were tested for linkage in 31 F(2) exencephalic embryos. Finally, 12 males, SS or LL for the Chr 13 region on an LM/Bc background, were testcrossed by SELH/Bc. RESULTS: The exencephaly frequencies in the F(1) (0.3%), BC(1) (4.4%), and F(2) (3.7%), and the distribution of F(2) males' testcross values (0-15.5%), indicated that the high risk of exencephaly in SELH/Bc is due to the cumulative effect of two or three loci. Linkage studies indicated the location of semidominant exencephaly-risk genes on Chr 13 near D13Mit13 (P < 0.001), Chr 5 near D5Mit168 (P < 0.025), and possibly Chr 11 near D11Mit10 (P < 0.07). The gene on Chr 13, Exen1, and the strong role of other loci were confirmed by the congenic males. CONCLUSIONS: The high risk of exencephaly in SELH/Bc mice is caused by the cumulative effect of two to three semidominant genes. Candidate genes include Msx2, Madh5, Ptch, and Irx1 (Chr 13) and Actb and Rac1 (Chr 5).

Molecular and phenotypic analysis of Attractin mutant mice.

Mutations of the mouse Attractin (Atrn; formerly mahogany) gene were originally recognized because they suppress Agouti pigment type switching. More recently, effects independent of Agouti have been recognized: mice homozygous for the Atrn(mg-3J) allele are resistant to diet-induced obesity and also develop abnormal myelination and vacuolation in the central nervous system. To better understand the pathophysiology and relationship of these pleiotropic effects, we further characterized the molecular abnormalities responsible for two additional Atrn alleles, Atrn(mg) and Atrn(mg-L), and examined in parallel the phenotypes of homozygous and compound heterozygous animals. We find that the three alleles have similar effects on pigmentation and neurodegeneration, with a relative severity of Atrn(mg-3J) > Atrn(mg) > Atrn(mg-L), which also corresponds to the effects of the three alleles on levels of normal Atrn mRNA. Animals homozygous for Atrn(mg-3J) or Atrn(mg), but not Atrn(mg-L), show reduced body weight, reduced adiposity, and increased locomotor activity, all in the presence of normal food intake. These results confirm that the mechanism responsible for the neuropathological alteration is a loss--rather than gain--of function, indicate that abnormal body weight in Atrn mutant mice is caused by a central process leading to increased energy expenditure, and demonstrate that pigmentation is more sensitive to levels of Atrn mRNA than are nonpigmentary phenotypes.

Linkage of otopalatodigital syndrome type 2 (OPD2) to distal Xq28: evidence for allelism with OPD1.

Otopalatodigital syndrome type 1 (OPD1) is an X-linked semidominant condition characterized by malformations of the skeleton, auditory apparatus, and palate. Previous studies have established linkage to a 16-cM region of Xq27-q28. A proposed allelic variant of OPD1, termed "OPD2," is associated with a more severe, frequently lethal phenotype with visceral and brain anomalies in addition to skeletal, auditory, and palatal defects. We report linkage of the OPD2 phenotype to a 2-cM region of distal Xq28 in a Maori kindred, with a maximum multipoint LOD score of 3.31 between the markers DXS1073 and DXS1108. This provides support for allelism between OPD1 and OPD2 and reduces the size of the disease interval to 1.8-2.1 Mb. We also demonstrate that female carriers of this disorder exhibit skewed inactivation that segregates with the high-risk haplotype and may be inversely related to the severity with which they manifest features of the disorder.

Neurodevelopmental outcome of infants treated with head cooling and mild hypothermia after perinatal asphyxia.

OBJECTIVES: To determine the neurodevelopmental outcome of infants treated with head cooling with systemic hypothermia after hypoxic-ischemic encephalopathy. STUDY DESIGN: Infants >/=37 weeks' gestation, who had an umbilical artery pH

A biochemical function for attractin in agouti-induced pigmentation and obesity.

Agouti protein, a paracrine signaling molecule normally limited to skin, is ectopically expressed in lethal yellow (A(y)) mice, and causes obesity by mimicking agouti-related protein (Agrp), found primarily in the hypothalamus. Mouse attractin (Atrn) is a widely expressed transmembrane protein whose loss of function in mahogany (Atrn(mg-3J)/ Atrn(mg-3J)) mutant mice blocks the pleiotropic effects of A(y). Here we demonstrate in transgenic, biochemical and genetic-interaction experiments that attractin is a low-affinity receptor for agouti protein, but not Agrp, in vitro and in vivo. Additional histopathologic abnormalities in Atrn(mg-3J)/Atrn(mg-3J) mice and cross-species genomic comparisons indicate that Atrn has multiple functions distinct from both a physiologic and an evolutionary perspective.

Delayed hypotension and subendocardial injury after repeated umbilical cord occlusion in near-term fetal lambs.

OBJECTIVE: This study was undertaken to determine whether myocardial injury occurs after repeated intrauterine asphyxia. STUDY DESIGN: Near-term fetal sheep with implanted instrumentation underwent either sham occlusions (n = 8) or repeated brief umbilical cord occlusions (n = 12) continued until the onset of severe (<20 mm Hg) or sustained hypotension. After 3 days of recovery, the fetal hearts were perfusion fixed. RESULTS: Repeated umbilical cord occlusions led to a severe metabolic acidosis (pH, 6.84 +/- 0.09; lactate concentration, 14.1 +/- 1.5 mmol/L) with increasing hypotension during occlusions, which were terminated after 128 +/- 38 minutes. After the occlusions, the mean arterial pressure showed a delayed fall, which resolved after 12 hours. Ultrastructural examination showed evidence of subendocardial injury, with dilatation of sarcoplasmic reticulum, margination and clumping of nuclear chromatin, and mitochondrial swelling. The most severe morphologic changes, including electron-dense mitochondrial inclusions, were found in the fetuses with delayed recovery of the fetal heart rate after the final occlusion. CONCLUSION: Subendocardial injury occurs after severe repeated intrauterine asphyxia in the late-gestation fetus, and this may contribute to cardiovascular compromise and the development of late decelerations.

Does early hospital discharge with home support of families with preterm infants affect breastfeeding success? A randomized trial.

UNLABELLED: The aim of the present study was to determine if earlier discharge of preterm infants (<37 wk) from hospital is safe and if it affects breastfeeding rates. In a pilot observational study, premature infants received full oral (sucking) feeds for a mean (SD) 7.7 +/- 7.9 d before discharge. In the main study, 308 preterm infants were randomly assigned to either Early Discharge (148 infants) when fully orally fed but not yet gaining weight or Routine Discharge (160 infants) when fully orally fed and also gaining weight before discharge. A further 122 mothers declined randomization. The Early Discharge group was followed by Visiting Nurse Specialists who were available 24 h a day, while the Routine group was followed by the Home Care Nurses available on week days. There were no significant differences between the groups in birthweight or gestational age. The Early Discharge group were discharged 2.5 +/- 2 d after full oral feeding compared to 4.4 +/- 2.7 d for the Routine group (p < 0.001) and 6.1 +/- 5 d for those who declined. However, there was no significant difference between the Early and Routine groups for breastfeeding either at discharge (80 vs 83%), or 6 wk (55 vs 60%) or 6 mo after discharge (36 vs 36%), or for weight gain, or rates of re-hospitalization (8.8% vs 11.9% at 6 wk, p = 0.37). CONCLUSION: Early discharge from hospital once a preterm infant can take full oral feeds does not alter later breastfeeding rates when adequate visiting nursing support is available.

Pregnancy outcome in women with reflux nephropathy and the inheritance of vesico-ureteric reflux.

In women with reflux nephropathy, we investigated whether pre-existing hypertension and impaired renal function influence the rates of preeclampsia, renal function deterioration and preterm birth. The infants were investigated for vesico-ureteric reflux (VUR). A prospective audit of 54 pregnancies in 46 women with reflux nephropathy was performed. Preeclampsia complicated 24% of pregnancies and was increased in women with pre-existing hypertension (42%) compared with normotensive women (14%), (RR 3.0 (95% CI 1.1-7.8)). Nine (18%) women experienced deterioration in renal function during pregnancy Women with mild or moderate renal impairment were at increased risk of renal function deterioration (RR 12.7 (95% CI 1.6-98.5); RR 19.8 (95% CI 2.6-155)), respectively A third of infants were delivered preterm. The risk of preterm birth was increased if the mother had pre-existing hypertension (p = 0.01) or moderate renal impairment (p = 0.002). Seventeen (43%) of the 40 infants who underwent micturating cystourethrography had VUR, consistent with autosomal dominant inheritance with reduced penetrance. In reflux nephropathy, pre-existing hypertension was associated with an increased risk of preeclampsia and pre-existing renal impairment with deterioration in renal function. Infants of women with reflux nephropathy should be screened for VUR.

Biochemical and genetic studies of pigment-type switching.

Mutations that affect the balance between the synthesis of eumelanin and pheomelanin provide a powerful set of tools with which to understand general aspects of cell signaling. Previous work from our laboratory has demonstrated that pheomelanin synthesis is triggered by the ability of Agouti protein to inhibit signaling through the Melanocortin 1 receptor (Mc1r). In a bioassay based on the Xenopus Mc1r, Agouti protein has two effects, competitive inhibition of receptor occupancy by alpha-MSH and down-regulation of receptor signaling, which are mediated separately by domains in the amino- and carboxy-terminal regions of Agouti protein, respectively. Recently, we have used the genetics of pigmentation as an in vivo system to screen for and analyze other mutations in the Agouti-melanocortin pathway. The pigmentary effects of Agouti are suppressed by the previously existing coat-color mutations mahogany (mg), mahoganoid (md), and Umbrous (U). Double mutant studies, with animals deficient for the Mc1r or those which carry Ay, indicate that mg and md are genetically upstream of the Mc1r, and can suppress the effects of Ay on both pigmentation and body weight. Positional cloning has recently identified the gene mutated in mahogany as a single transmembrane-spanning protein whose ectodomain is orthologous to human Attractin (Atrn).

Secreted and membrane attractin result from alternative splicing of the human ATRN gene.

Attractin, initially identified as a soluble human plasma protein with dipeptidyl peptidase IV activity that is expressed and released by activated T lymphocytes, also has been identified as the product of the murine mahogany gene with connections to control of pigmentation and energy metabolism. The mahogany product, however, is a transmembrane protein, raising the possibility of a human membrane attractin in addition to the secreted form. The genomic structure of human attractin reveals that soluble attractin arises from transcription of 25 sequential exons on human chromosome 20p13, where the 3' terminal exon contains sequence from a long interspersed nuclear element-1 (LINE-1) retrotransposon element that includes a stop codon and a polyadenylation signal. The mRNA isoform for membrane attractin splices over the LINE-1 exon and includes five exons encoding transmembrane and cytoplasmic domains with organization and coding potential almost identical to that of the mouse gene. The relative abundance of soluble and transmembrane isoforms measured by reverse transcription-PCR is differentially regulated in lymphoid tissues. Because activation of peripheral blood leukocytes with phytohemagglutinin induces strong expression of cell surface attractin followed by release of soluble attractin, these results suggest that a genomic event unique to mammals, LINE-1 insertion, has provided an evolutionary mechanism for regulating cell interactions during an inflammatory reaction.

Neonatal micrognathia is associated with small upper airways on radiographic measurement.

In order to determine if infants with clinical micrognathia identified in the newborn period have smaller upper airways than do normal infants, and if their airway size is related to risk of later apnoea, respiration-timed upper airway radiographic measurements were performed in 21 asymptomatic neonates with clinical micrognathia. Their radiographic measurements were compared with those of a previously reported cohort of 35 normal infants. The micrognathic infants and a control group of 27 infants referred for parental anxiety were followed for 6 mo on home apnoea monitors. Sleep apnoea at home requiring stimulation by the parents occurred in 6 of 7 infants with micrognathia associated with craniofacial anomalies, 9 of 14 (64%) infants with isolated micrognathia, but only 1 of the 27 control infants (p < 0.001). Upper airway measurements at term of the infants with isolated micrognathia who later experienced apnoea were significantly smaller than either those of normal infants (p < 0.01) or of micrognathic infants who did not have apnoea requiring stimulation (p < 0.05). In conclusion, upper airway measurements on timed lateral radiographs in asymptomatic micrognathic infants at term (corrected age) revealed them to be smaller than those of normal infants. Narrower upper airways were associated with increased risk of subsequent apnoea requiring stimulation.

Mahogany/attractin: en route from phenotype to function.

The mouse mahogany mutation affects melanocortin signaling pathways that regulate energy homeostasis and hair color. The gene mutated in mahogany mice encodes attractin, a large transmembrane protein that is broadly expressed and conserved among multicellular animals. Mouse attractin is likely to have additional roles outside melanocortin signaling, and cloning of the gene provides information that can be used to form testable hypotheses about its biochemical function.

Is changing the sleep environment enough? Current recommendations for SIDS.

Sudden infant death syndrome (SIDS or cot death) was the major cause of post-neonatal infant death in many countries in the late 1970s and 1980s. There is now very strong evidence that public intervention campaigns targeting the prone sleeping position, which had been identified by epidemiological studies as a major risk factor, were followed by substantial falls in the rate of SIDS. In the present review we discuss the evidence on which current recommendations for the prevention of SIDS are based. The prone sleeping position is now clearly causally associated with SIDS. Further reductions in SIDS may be produced by recommending the back sleeping position as opposed to the side position. Maternal smoking in pregnancy and bed sharing by infants of mothers who smoke are also strongly associated with SIDS, but have been harder to influence. Paternal smoking has also been implicated, although the magnitude of the reported risk is small. Finally, breastfeeding, pacifier use and having the infant sharing the parents bedroom, but not the bed, may also reduce risk. Continued reductions in SIDS mortality will require innovative public health education to target these major risk factors, while building on the "back to sleep" approach.